scholarly journals Investigation of the Combination of Pregabalin with Duloxetine or Amitriptyline on the Pharmacokinetics and Antiallodynic Effect During Neuropathic Pain in Rats

2021 ◽  
pp. E511-E520

BACKGROUND: Amitriptyline, duloxetine, and pregabalin are among the most pharmacotherapeutic, effective treatments for neuropathic pain control. However, the evaluation of synergism by combining these treatments is still poorly investigated. OBJECTIVES: To evaluate the pharmacokinetics of the combination of pregabalin plus duloxetine and pregabalin plus amitriptyline, as well as the effect of these on neuropathic pain on rodent model. STUDY DESIGN: The experimental study. SETTING: The research took place in the research laboratories at the Federal University of Alfenas after ethics committee approval. METHODS: This study used male Wistar rats weighing between 220 and 250 g. The animals were randomly divided into the following groups: monotherapy (pregabalin, amitriptyline, duloxetine), combined therapy (pregabalin + amitriptyline, pregabalin + duloxetine), and vehicle (ultrapure water). Pharmacokinetic analysis of pregabalin or combination (pregabalin + amitriptyline or pregabalin + duloxetine) in the plasma were performed by ultraperformance liquid chromatography tandem mass spectrometry. Neuropathic pain was induced by sciatic nerve constriction (chronic constriction injury [CCI]) model, and nociceptive threshold was measured by von Frey filaments test. In addition, to evaluate the influence of the treatments on the motor coordination, the rotarod test was used. RESULTS: The pharmacokinetic disposition of pregabalin was changed in the association with amitriptyline, presenting a clearance reduction and consequently an increase in bioavailability. Furthermore, after the 14th day of CCI, pregabalin was administered orally and induced antiallodynic effect after 1, 2:15, 4, and 8 hours of its administration and showed the greatest antiallodynic effect after 4 hours of its administration. Moreover, this effect was prolonged (up to 8 hours) by combination with amitriptyline. Additionally, pregabalin and pregabalin + duloxetine showed a hypoalgesic effect in sham rats. In addition, the rotarod test results showed that drugs did not influence the motor coordination of the rats. LIMITATIONS: Potential competition mechanisms during the excretion of pregabalin, when pregabalin was combined with amitriptyline, were not investigated in this study. CONCLUSIONS: The data demonstrated that combined therapy of pregabalin plus amitriptyline improved the bioavailability of pregabalin and potentiated the efficacy of the antiallodynic effect of pregabalin alone, proving to be advantageous for the treatment of sciatic neuropathic pain. KEY WORDS: Neuropathic pain, pregabalin, duloxetine, amitriptyline, pharmacokinetic, antiallodynic effect, combined therapy, rats

2021 ◽  
pp. 147565
Author(s):  
Opeyemi Samson Osuntokun ◽  
Busayo Grace Akingboye ◽  
Gbola Olayiwola ◽  
Taiwo Adekemi Abayomi ◽  
Abiodun Oludele Ayoka

2009 ◽  
Vol 19 ◽  
pp. S275-S276
Author(s):  
A. Onal ◽  
G. Kayalioglu ◽  
A. Parlar ◽  
A. Keser ◽  
S. Ulker

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Alexia Chauzy ◽  
Isabelle Lamarche ◽  
Christophe Adier ◽  
William Couet ◽  
Sandrine Marchand

ABSTRACT The purpose of this study was to investigate aztreonam (ATM) and avibactam (AVI) distribution in intraperitoneal fluid and muscle interstitial fluid by microdialysis in rats, with or without peritonitis, and to compare the unbound concentrations in tissue with the unbound concentrations in blood. Microdialysis probes were inserted into the jugular veins, hind leg muscles, and peritoneal cavities of control rats (n = 5) and rats with intra-abdominal sepsis (n = 9) induced by cecal ligation and punctures. ATM and AVI probe recoveries in each medium were determined for both molecules in each rat by retrodialysis by drug. ATM-AVI combination was administered as an intravenous bolus at a dose of 100-25 mg · kg−1. Microdialysis samples were collected over 120 min, and ATM-AVI concentrations were determined by liquid chromatography-tandem mass spectrometry. Noncompartmental pharmacokinetic analysis was conducted and nonparametric tests were used for statistical comparisons between groups (infected versus control) and medium. ATM and AVI distribution in intraperitoneal fluid and muscle was rapid and complete both in control rats and in rats with peritonitis, and the concentration profiles in blood, intraperitoneal fluid, and muscle were virtually superimposed, in control and infected animals, both for ATM and AVI. No statistically significant difference was observed between unbound tissue extracellular fluid and systemic areas under the curve for both molecules in control and infected animals. In the present study, intraperitoneal infection induced by cecal ligation and puncture had no apparent effect on ATM and AVI pharmacokinetics in rats.


2021 ◽  
Vol 15 (2) ◽  
pp. 110-121
Author(s):  
Dan Alexandru SZABO ◽  
◽  
Andreea Roxana UJICĂ ◽  
Ovidiu URSU ◽  
◽  
...  

The present study aimed to debate a topic less addressed by most people, which involved research on a group of 20 students from rural areas, aged 10–14 years, which consists of performing two tests, namely the Ruler drop test and the Hand-eye coordination test, which aims at the reaction speed of the dominant and non-dominant hand and also the hand-eye coordination capacity of the subjects. The paper aimed to identify whether somatic factors and age influence the results of the group. In order to perform the two tests, it was necessary, for the beginning, information related to the study group, information on weight, age, height, dominant hand, respectively dominant eye. These represented the point of interest of the research, being reported individually to the test results, thus constituting the study basis of statistics. After obtaining the results, we concluded that a significant significance is encountered when comparing the dominant hand with the non-dominant one, obtaining a positive value for the dominant hand. At the same time, we interpreted after the research that females tend to have a much faster reaction speed, more significant than the males when it comes to using the non-dominant hand. The hypothesis was confirmed, with differences in somatic factors’ influence, but the others do not show significant values except those stated above. In addition to the practical part, the research involves an interesting theoretical foundation being reached aspects related to proprioception, coordination, speed, ways of using tests, and the opinion of other researchers who have conducted similar studies.


2020 ◽  
Vol 15 (1) ◽  
pp. 86-97
Author(s):  
Hafshah . ◽  
Kristina Simanjuntak

The sufferers of Diabetes Mellitus (DM) in Indonesia is the highest with fourth number in the world, with a mortality rate of 1.2 million in 2012. Because of it, DM research using antihyperglycemic green tea is needed. This study aims to determine the effectiveness of green tea extracts on decreasing fasting blood glucose (KGDP) levels in alloxan-induced white male Wistar rats. Samples were 30 male rats, aged 8-12 weeks, weight ± 200 grams. Rats were grouped into 6 groups with the first group (K1) as a control, the second group (K2) induced alloxan, the third group (K3) induced alloxan with glibenclamide, the fourth group (K4), the fifth group (K5), and the sixth group (K6) induced alloxan with green tea extract as the treatment with dose of green tea extract, 200 mg/kg, 400 mg/kg, and 800 mg/kg. The first, FBG level examination is done 3 days after induction of alloxan using a glucometer. Giving green tea extract was given for 16 days orally, then FBG level re-examined from the tail of rats. One Way ANOVA Test Results, there is the effectiveness of green tea extract on reducing FBG level (p = 0,000). The post hoc Bonferroni test showed that giving 800 mg/kg of green tea extract was the best dose in reducing KGDP close to normal (p = 0,000).


Author(s):  
О. В. Іващенко ◽  
Т. В. Карпунець ◽  
Ю. В. Крінін

Purpose — to identify patterns of age dynamics of functional and motor fitness girls eighth and ninth grades.Material and methods. To achieve the objectives adopted the following methods: analysis of scientific literature, teacher testing and treatment methods of mathematical statistics research results. In the study involved 14 dyvchat class 8, 14 — 9 class.Conclusions. Analysis of the test results shows that statistically significant differences between girls 8 and 9 classes in functional samples was observed. For the functional state of respiration and circulation girls 8 and 9 classes are rated as healthy untrained.Girls 9 classes show statistically significantly better results in tests for speed strength, static display of strength and motor coordination (tests 8 «Long jump from place, see» 7 «Height in folded hands, p ‘and 2’ Evaluation of temporal parameters movement, with error «).Standardized canonical discriminant function coefficients can determine the value contribution of variables in the function result. With the largest contribution to the canonical function variables are 6, 10 and 7: the higher the value of these variables, the more important functions. The foregoing indicates to assess the functional and motor fitness of students grades 8—9 using the proposed battery of tests.Structural factors canonical discriminant function shows that feature most significantly associated with 7, 8 and 2 variables: the more attention is paid to static, the actual strength and coordination training, the greater the likelihood of increasing the level of functional and motor fitness girls 8—9 grades.100.0% initial observations are grouped correctly classified. Thus, the canonical discriminant function can be used for evaluation and prediction of functional and motor fitness girls 8—9 grades. 


1995 ◽  
Author(s):  
J.L. Brady ◽  
D.S. Wolcott ◽  
P.H. Daggett ◽  
J.F. Ferguson ◽  
J.L. Hare ◽  
...  

2021 ◽  
pp. 096452842110557
Author(s):  
Liaw Chao ◽  
Alexandre SR Gonçalves ◽  
Ana Carolina P Campos ◽  
Daniele V Assis ◽  
Rodrigo Jerônimo ◽  
...  

Background: Neuropathic pain (NP) is a complex disease that remains challenging to treat. Low-frequency dense-and-disperse (DD) electroacupuncture (EA) has been used as adjuvant therapy for neuropathic pain; however, its analgesic effect decreases as stimulation time increases, or when it is repeatedly used. We hypothesized that a new frequency parameter could improve the effectiveness of EA, and aimed to compare the efficacy and duration of the analgesic effect between classic DD-EA and non-repetitive and non-sequential frequency (random frequency (RF)-EA) in neuropathic rats. Furthermore, the effect of RF-EA at local traditional acupuncture point locations versus auricular vagus nerve stimulation (aVNS) was evaluated. Methods: Male Wistar rats with peripheral neuropathy were subjected to a single session of DD-EA or RF-EA for 20 or 40 min at ST36 + GB34. An additional group of rats was treated with RF-EA for 20 min using aVNS at the appropriate ear point locations. Paw pressure test, von Frey filaments and spontaneous pain scores were evaluated. Sham-operated rats were used as controls. Results: In all, 20 min of RF-EA reversed hyperalgesia (for 24 h) and allodynia (for 8 h), showing a longer analgesic effect than DD-EA. Both RF-EA and DD-EA induced partial inhibition of spontaneous pain for 8 h. Forty minutes of DD-EA did not interfere with the NP phenomena; however, RF-EA induced significant long-term analgesia. aVNS induced an analgesic effect similar to local stimulation. Conclusion: This pilot study shows that RF-EA at both local traditional acupuncture point and auriculotherapy point locations induces long-lasting analgesia in neuropathic rats, and more effectively so than classical DD-EA.


2019 ◽  
Vol 58 (1) ◽  
pp. 31-36
Author(s):  
Li Zhou ◽  
Wang Xi ◽  
Hui Zhang ◽  
Lili Sun ◽  
Jinlong Yu ◽  
...  

Abstract A simple and enantioselective method was developed and validated for the simultaneous determination of (R)- and (S)-trelagliptin in beagle dog plasma by chiral liquid chromatography tandem mass spectrometry. Trelagliptin enantiomers and (R)-rabeprazole (as internal standard, IS) were extracted from plasma samples by liquid–liquid extraction and separated on a CHIRALCEL OX-3R column using acetonitrile-5 ammonium bicarbonate as the mobile phase in gradient elution mode. The multiple reactions monitoring transitions of m/z 358.1→341.2 and 359.9→150.1 were used to quantify trelagliptin enantiomers and IS, respectively. This method was validated for sensitivity, specificity, linearity, precision, accuracy and stability of specific analytes under various conditions. And it was successfully applied to evaluating the pharmacokinetic profile of trelagliptin enantiomers in beagle dogs after single intravenous administration of (R)-trelagliptin injection (at 1 mg/kg) and oral administration (at 6.7 mg/kg). In this study, no chiral bioconversion of (R)-trelagliptin to (S)-trelagliptin in beagle dog plasma was observed. The absolute bioavailability of (R)-trelagliptin was identified to be 128.2%.


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